Environmental enrichment enhances conditioned place preference to ethanol via an oxytocinergic-dependent mechanism in male mice

Author(s)

Rae, Mariana ^{[1, 2]} ; Zanos, Panos ^{[1, 3]} ; Georgiou, Polymnia ^{[1, 3]} ; Chivers, Priti ^[1] ; Bailey, Alexis ^{[1, 4]} ; Camarini, Rosana ^[2]

Affiliation

^[1] Univ Surrey, Fac Hlth & Med Sci, Guildford, Surrey - England

^[2] Univ Sao Paulo, Dept Farmacol, BR-05508900 Sao Paulo, SP - Brazil

^[3] Univ Maryland, Sch Med, Dept Psychiat, Baltimore, MD 21201 - USA

^[4] St Georges Univ London, Inst Med & Biomed Educ, London - England

• Document type: Journal article
• Source: Neuropharmacology; v. 138, p. 267-274, AUG 2018.
• Web of Science Citations: 7

Abstract

Environmental conditions, such as stress and environmental enrichment (EE), influence predisposition to alcohol use/abuse; however, the underlying mechanisms remain unknown. To assess the effect of environmental conditions on the initial rewarding effects of alcohol, we examined conditioned place-preference (CPP) to alcohol following exposure to EE in mice. Since social context is a major factor contributing to initial alcohol-drinking, we also assessed the impact of EE on the levels of the ``social neuropeptide{''} oxytocin (OT) and its receptor, OTR. Finally, we assessed the effect of pharmacological manipulations of the oxytocinergic system on EE-induced alcohol CPP. While EE increased sociability and reduced anxiety-like behaviors, it caused a similar to 3.5-fold increase in alcohol reward compared to controls. EE triggered profound neuroadaptations of the oxytocinergic system; it increased hypothalamic OT levels and decreased OTR binding in the prefrontal cortex and olfactory nuclei of the brain. Repeated administration of the OT analogue carbetocin (6.4 mg/kg/day) mimicked the behavioral effects of EE on ethanol CPP and induced similar brain region-specific alterations of OTR binding as those observed following EE. Conversely, repeated administration of the OTR antagonist L,369-899 (5 mg/kg/day) during EE exposure, but not during the acquisition of alcohol CPP, reversed the pronounced EE-induced ethanol rewarding effect. These results demonstrate for the first time, a stimulatory effect of environmental enrichment exposure on alcohol reward via an oxytocinergic-dependent mechanism, which may predispose to alcohol abuse. This study offers a unique prospective on the neurobiological understanding of the initial stages of alcohol use/misuse driven by complex environmental-social interplay. (C) 2018 Elsevier Ltd. All rights reserved. (AU)

• FAPESP's process: 12/09854-0 - Effects of environmental enrichment on ethanol induced behaviors in Swiss mice: role of stress circuitry
• Grantee: Mariana Beu Rae
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 12/50207-8 - Effects and neurobiological mechanisms of environmental manipulations on ethanol and nicotine induced behavioural effects: involvement of the stress circuitry
• Grantee: Rosana Camarini
• Support Opportunities: Regular Research Grants
• FAPESP's process: 15/02397-0 - Study of environmental enrichment inducing a protective phenotype of behaviors that assess addictive features in mice
• Grantee: Rosana Camarini
• Support Opportunities: Regular Research Grants